Clin Exp Otorhinolaryngol.  2014 Mar;7(1):42-46.

Association Study of FOS-Like Antigen-2 Promoter Polymorphisms With Papillary Thyroid Cancer in Korean Population

• Kim SW
• Kim CD
• Chung JH
• Kwon KH

Abstract

OBJECTIVES
FOS-like antigen-2 (FOSL-2), a member of the FOS gene family, encode leucine zipper proteins that can heterodimerize with proteins of Jun family. Thus, activating protein (AP)-1 transcription factor is formed, has a crucial role in proliferation, differentiation and apoptosis of normal tissue as well as oncogenic transformation and progression. We performed an association study of single nucleotide polymorphisms (SNPs) in the FOSL-2 with papillary thyroid cancer (PTC). We also estimated the relationships between the SNPs and the clinicopathologic characteristics of PTC.
METHODS
One promoter SNPs (rs925255) of FOSL-2 gene were genotyped with direct sequencing method in 94 PTC and 213 controls. PTC patients were dichotomized and compared with respect to clinical parameters of PTC. Genetic data were analyzed using Helixtree, SNPAnalyzer, SNPStats. Multivariate logistic regression analysis was fulfilled to evaluate the genetic effect with adjustment for age and sex.
RESULTS
SNP (rs925255) in FOSL-2 showed a significant association (codominant 1 model [G/G vs. A/G]: odds ratio [OR], 0.531, 95% confidence interval [CI], 0.293 to 0.96, P=0.036; dominant model: OR, 0.50, 95% CI, 0.28 to 0.89, P=0.015) with PTC. The frequency of allele G in rs925255 was also significantly associated with PTC (OR, 0.59; 95% CI, 0.34 to 0.91; P=0.02). But we fail to prove significant association between this polymorphism (rs925255) and clinico-pathological parameters.
CONCLUSION
Our findings suggest that the rs925255 SNP and its allele G show significant association with the PTC in Korean population.

Keyword

Papillary thyroid cancer; FOS-like antigen-2; Polymorphism

MeSH Terms

Alleles
Apoptosis
Genes, fos
Humans
Leucine Zippers
Logistic Models
Methods
Odds Ratio
Polymorphism, Single Nucleotide
Thyroid Gland*
Thyroid Neoplasms*
Transcription Factors
Transcription Factors

Reference

1. Ministry for Health, Welfare and Family Affairs, National Cancer Information Center. Incidence rates of cancer [Internet]. Goyang: National Cancer Information Center;c2012. cited 2013 Nov 20. Available from: http://www.cancer.go.kr/cms/statics/incidence/index.html#2.

2. Zitzelsberger H, Bauer V, Thomas G, Unger K. Molecular rearrangements in papillary thyroid carcinomas. Clin Chim Acta. 2010; 3. 411(5-6):301–308. PMID: 19958753.

3. Baverstock K, Egloff B, Pinchera A, Ruchti C, Williams D. Thyroid cancer after Chernobyl. Nature. 1992; 9. 359(6390):21–22. PMID: 1522880.

4. DeLellis RA. Pathology and genetics of thyroid carcinoma. J Surg Oncol. 2006; 12. 94(8):662–669. PMID: 17131411.

5. Czene K, Lichtenstein P, Hemminki K. Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer. 2002; 5. 99(2):260–266. PMID: 11979442.

6. Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst. 1994; 11. 86(21):1600–1608. PMID: 7932824.

7. Young MR, Colburn NH. Fra-1 a target for cancer prevention or intervention. Gene. 2006; 9. 379:1–11. PMID: 16784822.

8. Chiappetta G, Tallini G, De Biasio MC, Pentimalli F, de Nigris F, Losito S, et al. FRA-1 expression in hyperplastic and neoplastic thyroid diseases. Clin Cancer Res. 2000; 11. 6(11):4300–4306. PMID: 11106247.

9. Smith M, Burke Z, Humphries A, Wells T, Klein D, Carter D, et al. Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression mediated by dominant negative Fra-2. Mol Cell Biol. 2001; 6. 21(11):3704–3713. PMID: 11340164.

10. Milde-Langosch K, Janke S, Wagner I, Schroder C, Streichert T, Bamberger AM, et al. Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility. Breast Cancer Res Treat. 2008; 2. 107(3):337–347. PMID: 17393299.

11. Murakami M, Ui M, Iba H. Fra-2-positive autoregulatory loop triggered by mitogen-activated protein kinase (MAPK) and Fra-2 phosphorylation sites by MAPK. Cell Growth Differ. 1999; 5. 10(5):333–342. PMID: 10359014.

12. Bakiri L, Matsuo K, Wisniewska M, Wagner EF, Yaniv M. Promoter specificity and biological activity of tethered AP-1 dimers. Mol Cell Biol. 2002; 7. 22(13):4952–4964. PMID: 12052899.

13. Handkiewicz-Junak D, Czarniecka A, Jarzab B. Molecular prognostic markers in papillary and follicular thyroid cancer: current status and future directions. Mol Cell Endocrinol. 2010; 6. 322(1-2):8–28. PMID: 20138116.

14. Eun YG, Shin IH, Kim MJ, Chung JH, Song JY, Kwon KH. Associations between promoter polymorphism -106A/G of interleukin-11 receptor alpha and papillary thyroid cancer in Korean population. Surgery. 2012; 2. 151(2):323–329. PMID: 21982075.

15. Dardano A, Falzoni S, Caraccio N, Polini A, Tognini S, Solini A, et al. 1513A>C polymorphism in the P2X7 receptor gene in patients with papillary thyroid cancer: correlation with histological variants and clinical parameters. J Clin Endocrinol Metab. 2009; 2. 94(2):695–698. PMID: 19017759.

16. Ozgen AG, Karadeniz M, Erdogan M, Berdeli A, Saygili F, Yilmaz C. The (-174) G/C polymorphism in the interleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish patients. J Endocrinol Invest. 2009; 6. 32(6):491–494. PMID: 19494710.

17. Erdogan M, Karadeniz M, Ozbek M, Ozgen AG, Berdeli A. Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population. J Endocrinol Invest. 2008; 9. 31(9):750–754. PMID: 18997484.

18. Siraj AK, Al-Rasheed M, Ibrahim M, Siddiqui K, Al-Dayel F, Al-Sanea O, et al. RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population. J Endocrinol Invest. 2008; 10. 31(10):893–899. PMID: 19092295.

19. Rebai M, Kallel I, Charfeddine S, Hamza F, Guermazi F, Rebai A. Association of polymorphisms in estrogen and thyroid hormone receptors with thyroid cancer risk. J Recept Signal Transduct Res. 2009; 29(2):113–118. PMID: 19519176.